Activin is a pluripotent hormone/growth factor that is involved in important biological functions including reproduction, development, and cell differentiation and survival. This Project studies the molecular events that lead to signal propagation by this protein. Activin interacts with two classes of cell surface mutant activin molecules to study the events that initiate signal transduction. We will employ X-ray crystallographic and mutagenesis data obtained by this Program to design these mutants. The initial interaction with activin type II receptors will be analyzed in detail. The mechanism of interaction with type I regulation of these events will be investigated. To further our understanding of the specific activities of the related proteins activin and TGFbeta, we will generate chimeric molecules and test these in biological systems specific for each of these factors.